Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice

Interferon alpha/beta plays an important role in the first-line defense aga inst viral infections and can modulate cytokine responses by T-helper cells . Type 1 interferons (IFNs) are clinically important in infectious diseases and in the treatment of leukemia and lymphomas. Many different cell types have the capacity to produce IFN-alpha after encounter with virus and bacte ria. The major, natural type 1 IFN-producing cell in humans was recently de scribed as the plasmacytoid T cell, or pDC2, and it can differentiate into dendritic cells (DCs) on culture. This study describes the murine natural I FN-alpha -producing cell, or pDC2, that shares morphologic features with it s human counterpart but has some distinct phenotypical characteristics. Mur ine plasmacytoid DCs can be differentially isolated based on their expressi on of CD11c, B220 (CD45R), and Thy1.2 (CD90). They lack expression of myelo id (eg, CD11b) antigens and CD8 alpha, a marker used to isolate lymphoid DC s. Like human pDC2, murine plasmacytoid DCs exhibit their maximal type 1 IF N-producing capacity at a precursor stage; pDCs isolated from bone marrow r esponded to viral stimulation with higher IFN-alpha production than cells o f the same phenotype isolated from spleen. Mobilization of mice with Flt3 l igand (Flt3L) or Flt3L and granulocyte-macrophage colony-stimulating factor , hematopoietic factors that specifically enhance DC growth, resulted in st rikingly Increased numbers of pDC In bone marrow and spleen. The isolation of this novel murine DC subset may serve as a useful tool In the study of v iral immunobiology and for the design of treatments for murine malignancies . (C) 2001 by The American Society of Hematology.